Melanocyte Stimulating Hormone

Melanocyte stimulating hormones , also known collectively as MSH , melanotropins or intermedins , are a family of peptide hormones and neuropeptides consisting of α-melanocyte stimulating hormone (α-MSH), β-melanocyte stimulating hormone ( β-MSH), and -melanocyte-stimulating hormone (γ-MSH) which are produced by cells in the pars intermedia of the anterior lobe of the pituitary gland. Synthetic analogues of α-MSH, such as afamelanotide (Melanotan I; Scenesse), Melanotan II , and bremelanotide (PT-141), have been developed and researched.


Different forms of MSH arise from different cleavages of the propiomelanocortin protein, which also produces other important neuropeptides such as adrenocorticotropic hormone .

Melanocytes in the skin make and secrete MSH in response to ultraviolet light, where it increases the synthesis of melanin . Some neurons in the arcuate nucleus of the hypothalamus secrete α-MSH in response to the producer and leptin ;α-MSH is also produced and secreted in the anterior lobe of the pituitary gland.


Acting through the melanocortin 1 receptor, α-MSH stimulates the production and release of melanin (a process called melanogenesis) by melanocytes in the skin and hair.

Acting in the hypothalamus, α-MSH suppresses appetite. α-MSH is secreted in the hypothalamus which also contributes to sexual arousal.

In amphibians

In some animals (such as the claw-toe frog Xenopus laevis ) MSH production increases when the animal is in a dark place. This causes the pigment to diffuse into the pigment cells in the toad’s skin, making it darker, and harder for predators to detect. Pigment cells are called melanophores and therefore, in amphibians, the hormone is often referred to as melanophore-stimulating hormone.

In humans

An increase in MSH will also cause darkening of the skin in humans. MSH increases in humans during pregnancy. This, along with increased estrogen, causes an increase in pigmentation in pregnant women. Cushing’s disease caused by excess adrenocorticotropic hormone (ACTH) can also result in hyperpigmentation such as, axillary nigricans in the axillae. Most people with primary Addison’s disease have darkening of the skin (hyperpigmentation), including areas not exposed to the sun; Typical spots are skin creases (such as on the hands), nipples, and the inside of the cheeks (buccal mucosa), with newer scars becoming hyperpigmented, while older ones do not. This is because MSH and ACTH share the same precursor molecule, propiomelanocortin (POMC).

Different levels of MSH are not the main cause of variation in skin color. However, many red-headed people, and others who do not tan well, have variations in their hormone receptors, causing them not to respond to MSH in the blood.

Structure of MSH. 

The different forms of MSH belong to a group called melanocortins. This group includes ACTH, α-MSH, β-MSH, and -MSH; These peptides are all cleavage products of a larger precursor peptide called propiomelanocortin (POMC). α-MSH is the most important melanocortin for pigmentation.

The different forms of MSH contain the following amino acid sequences:

β-MSH (Human):Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp
β-MSH (porcine):Asp-Glu-Gly-Pro-Tyr-Lys-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp
Melanocyte Stimulating Hormone

Synthetic MSH

Synthetic analogues of α-MSH have been developed for human use. Two of the better known are afamelanotide (Melanotan I) in testing by Clinuvel Pharmaceuticals and bremelanotide by Palatin Technologies. Others include Modimelanotide and Setmelanotide.

  • Afamelanotide (brand name Scenesse) has been approved for the treatment of erythropoietic protoporphyria in Europe and is also being investigated as a method of photoprotection in the treatment of polymorphic light eruptions, actinic keratosis and squamous cell carcinoma (a type of skin cancer ). [6]
  • An additional analog called Melanotan II caused increased libido and erections in most male test subjects and arousal with associated genital involvement in most female test subjects. [7] Bremelanotide (formerly PT-141) which stemmed from Melanotan II research, is currently under development for its aphrodisiac effects. These effects are mediated by actions in the hypothalamus on neurons that express MC3 and MC4 receptors.

What is melanocyte-stimulating hormone?

Melanocyte-stimulating hormones are peptide hormones that perform various functions. Among other things, they are responsible for the formation of melamine. To perform their functions, they dock on so-called melanocortin receptors. Melanocortin receptors are G-protein coupled receptors. These are membrane-bound receptors that, with the help of GTP-binding proteins , conduct signals into the cell, where they stimulate the initiation of various reactions. Melanocyte-stimulating hormone , also known as melanotropin, consists of three different peptide hormones. These are alpha- beta- and gamma-MSH. All three MSH hormones are made from adrenocorticotropin (with) the prohormone propiomelanocortin (POMC) ACTH) and beta-endorphins. All MSH and ACTH dock on the same melanocortin receptors MC1R, MC2R, MC3R, MC4R and MC5R to exert their effects.

function, action and role

The function of melanocyte-stimulating hormone involves stimulating melanocytes to produce melanin . Especially in the presence of increased ultraviolet radiation from the sun, there is an increase in the production of MSNH in order to provide better sun protection to the brow skin . In addition to melanin production, MSH also regulates the fever response and stimulates the appetite center. To mediate these actions, MSH must couple to melanocortin receptors. Individual receptors each mediate their own actions. Melanocortin receptor 1 (MC1R) regulates hair color and skin tanning. The action of the melanocortin receptor 2 (MC2R) mediatesACTH . Another melanocortin receptor, MC3R, is expressed in brain , placenta , or intestinal tissue. It is not found in melanocytes or the adrenal cortex. This receptor, with the help of MSH, controls the lowering of the fever response and food utilization, reducing the storage of body fat. MC4R is also expressed in brain , placenta and intestinal tissues and, with the help of MSH, slightly increases body temperature while suppressing the fever response. In addition, the appetite response is suppressed, metabolic energy consumption is affected, and sexual desire is increased. Melanocyte-stimulating hormones are released when needed. They are firmly integrated into the regulator circuitendocrine system . When there is a high demand for ACTH, a higher amount of alpha-MSH is also produced at the same time. ACTH controls the production of glucocorticoid hormones. Thus, it responds to the greater demand for these hormones. At the same time, more MSH is also produced.

Formation, occurrence, properties and optimum level

Melanocyte-stimulating hormones are produced in the hypothalamus or pituitary intermediate lobe. There, they are formed by the degradation of the prohormone propiomonoelocortin (POMC). POMC initially gives rise to ACTH, gamma-MSH and beta-lipotropin. In the process, alpha-MSH can form from ACTH through a further cleavage of the peptide residue. Beta-lipotropin is broken down into gamma-lipoproteins and beta-endorphins. Finally, beta-MSH is then formed from gamma-lipotropin.

diseases and disorders

As mentioned earlier, melanocyte-stimulating hormone, abbreviated as PhC, along with ACAN and beta-endorphins, are formed from the prohormone propiomonocortin. Propiomelanocortin is made up of 267 amino acids . Since this hormone is a prohormone, it must remain intact to be broken down into an effective hormone. The coding gene propiomelanocortin is located on chromosome 3. There is a known clinical picture based on the mutation of this gene . Affected individuals suffer from severe obesity and renal insufficiency at an early age. He also has a red hair color. Due to defective formation of MSH, they can no longer carry out their functions properly. Vast obesity , due to disturbance of the appetite center and regulation of energy consumptiondevelops. In addition, the formation of melanin is also disturbed. This causes red hair . While the hormone ACTH is also missing, the adrenal cortex may no longer be optimally stimulated. Mutations on individual receptors can also cause partial MSH functions to fail, as they can no longer dock to the respective receptor. In other hormone-related diseases, melanocyte-stimulating hormones play only a minor role. However, they may contribute to the typical symptoms of these diseases. Specifically in the context of Addison’s disease , there is a symptom indicating an increased concentration of MSH. Addison’s diseaseOften characterized by a bronze discoloration of the skin. Here, melanin is rapidly formed, which accumulates in the skin. Generally, a brown discoloration of the skin is seen as a sign of health . In Addison’s disease, however, it has a serious basis. Addison’s disease is a serious hormonal disorder that often leads to death from organ failure. For some reason, the adrenal cortex is destroyed in this disease. This may be due to autoimmune processes, injury to this area, or other reasons. In any case, the production of the glucocorticoids cortisol , aldosterone and sex hormones can only be done to a lesser extent. This gives the main symptoms of this disease. However, since the hormonal system is subject to a regulatory mechanism, the hypothalamusIt is stimulated to produce more ACTH. However, even an increased ACTH concentration cannot stimulate the formation of glucocorticoids because the adrenal glands are destroyed. In addition to increased formation of ACTH, melanocyte-stimulating hormone also increases. Melanocytes are stimulated to produce more melanin.